Absorption of any molecule, such as a nutrient or pharmaceutical agent, from the oral cavity and more specifically from the lingual and sub-lingual regions involves a different route than absorption of molecules through the gastrointestinal tract. Molecules absorbed from the stomach and small intestines of the gastro-intestinal tract are collected in the hepatic portal drainage system and go directly to the liver where they are exposed to a variety of enzymes which degrade many therapeutics and nutrients, including peptides, proteins and oligonucleotides. In contrast, molecules absorbed from the oral, lingual and sub-lingual regions go directly into the systemic circulation, bypassing the hepatic portal system and avoiding initial exposure to the enzymes in the gastrointestinal tract. The oral cavity is a far gentler environment for many molecules, especially peptides and proteins, compared to the harsh acidic and peptide lysing environment of the stomach and intestines. Furthermore, the underside and base of the tongue, as well as the base of the oral cavity beneath the tongue, are highly variegated ad vascularized, containing capillaries close to the surface, which presents a considerable surface area to allow rapid absorption of a desired drug or nutrient.
For the above reasons, the oral cavity and more specifically, the lingual and sub-lingual regions of the oral cavity, appear to be an idea site for the delivery of many therapeutic and nutritional molecules, including peptides and proteins. However, while a number of drugs have been successfully delivered by this route, there remain a number of problems with this mode of delivery.
One problem with using the oral cavity for drug delivery is due to a patient's automatic swallowing response. A liquid placed in the oral cavity in amounts greater than 200 microliters (μL) will usually elicit a swallowing response, removing the drug to be delivered from the oral cavity and subjecting it to the harsh conditions of the stomach. As a result, most of the drug delivered to the buccal cavity is no longer available for absorption from the oral, lingual and sub-lingual regions. This reduces the bioavailability of the drug.
Attempts have been made to overcome this problem by affixing the drug to a film or other adhesive that adheres to the sublingual space, trapping the drug next to the absorptive surface. However, this approach presents many limitations. For example, a film or patch utilizes only a limited amount of the potential surface area that is available for absorption, which thereby reduces the amount of drug that can be delivered. Additionally, the base of the tongue is irregularly shaped and variegated and as a result standardized patches do not readily adhere to it. Further, an individual who has a foreign substance located under the tongue normally automatically reacts by moving the position of the foreign substance and swallow it.
Therefore it is an object of the invention to provide a device for administering drugs to the oral cavity, particularly the sub-lingual region.
It is a further object of the invention to provide improved bioavailability for oral drug delivery.